Methods for minimally invasive, non-permanent occlusion of a uterine artery

ABSTRACT

Non-permanent occlusion of the uterine arteries is sufficient to cause the demise of uterine myomata without unnecessarily exposing other tissues and anatomical structures to hypoxia attendant to prior permanent occlusion techniques. A therapeutically effective transient time of occlusion of a uterine artery to treat uterine fibroid tumors is from 1 hours to 24 hours, and preferably is at least about 4 hours. A therapeutically effective temporary time of occlusion of a uterine artery to treat uterine fibroid tumors is from 1 day (24 hours) to 7 days (168 hours), and preferably is about 4 days (96 hours). By invaginating the tissues of the vaginal wall up to or around a uterine artery, collapse of the uterine artery can be achieved without penetrating tissue of the patient.

This application is a divisional of copending application Ser. No.09/908,815 filed Jul. 20, 2001, which is a continuation of co-pendingapplication Ser. No. 09/556,934 filed Apr. 20, 2000, now U.S. Pat. No.6,550,482 and which claims priority to provisional application Ser. No.60/279,477 filed Mar. 28, 2001, all of which are incorporated herein byreference in their entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to the treatment of disorderswhich receive blood flow from the uterine arteries, and moreparticularly to methods for the non-permanent occlusion of the uterineartery or arteries, including for use in treating uterine myomata(fibroids), dysfunctional uterine bleeding (DUB), post partumhemorrhaging (PPH), and uterine bleeding associated with cesariansection surgery.

2. Brief Description of the Related Art

Hysterectomy (surgical removal of the uterus) is performed onapproximately 600,000 women annually in the United States. Forapproximately 340,000 women, hysterectomy is probably the best currenttherapeutic choice for the treatment of their diseases (uterine cancer,endometriosis, menorrhagia, and prolapse). For approximately 60,000women with dysfunctional uterine bleeding (abnormal menstrual bleedingthat has no discrete anatomic explanation such as a tumor or growth),newer endometrial ablation techniques may be an alternative tohysterectomy. For approximately 200,000 women with benign butsymptomatic (excessive bleeding, pain, and “bulk” sensations) musculartumors of the uterus, known as leiomyoma or fibroids, newer treatmentmethods have been developed which may spare these women a hysterectomy,as well.

Hysterectomy for treating uterine fibroid disorders, though effective,has many undesirable characteristics. Thus, any method which canapproximate the therapeutic result of a hysterectomy without removingthe uterus (and commonly the ovaries since they are closely adjacent tothe uterus) would be a significant improvement in this field.

The undesirable characteristics of hysterectomy include a knownmortality rate of 0.5 deaths per 1000 hysterectomies. Stated anotherway, the risk of death within 30 days of hysterectomy is thirty timesgreater for women who have had a hysterectomy than for women of similarages and backgrounds who have not had a hysterectomy. Morbidity (medicalsymptoms and problems short of death) associated with hysterectomyinclude possible injury to adjacent organs (the bladder, the ureters,and bowel), hospital stay of approximately one week, five to six weeksof slow recovery to normal activity, three weeks of absence from work,direct medical expenses of at least $10,000, indirect cost of time awayfrom work, a future three-fold increase in the incidence ofcardiovascular disease, decreased sexual pleasure in approximatelythirty percent of women, and depression and anxiety for many years afterthe hysterectomy for approximately eight percent of women.

Surgically removing fibroids (myomectomy) or in situ ablation of uterinefibroids is a bit like eradicating ants in the pantry—they are not allseen from one perspective and there may be a lot of them. Commonly, adiagnosis of uterine fibroids involves the presence of multiplefibroids, often averaging ten fibroids or more per afflicted uterus.Consequently, it is difficult to know which fibroid is causing symptomsto the patient (bleeding, pain, and bulk effects on adjacent organs).Furthermore, fibroids occur at different layers in the uterus. Uterinefibroids can occur adjacent to the lining of the uterus (submucosalfibroid), in the myometrium (intramural fibroid), or adjacent to theouter layer of the uterus (subserosal fibroid). Consequently, if one isdirectly observing the uterus from the peritoneal cavity, onlysubserosal fibroids would be seen. If one is directly observing theuterus from the endometrial surface of the uterus, only the submucosalwould be seen. Fibroids deep within the wall of the uterus are poorlyvisualized from either surface. Finally, since fibroids come in allsizes, only the larger fibroids will be seen in any case.

Clearly, the strategy of identifying which individual fibroid is causingsymptoms (when there are often many), finding that fibroid, and theneither removing or destroying that individual fibroid is a rathercomplex strategy. It is therefore easy to understand why thehysterectomy is such a common surgical choice. With hysterectomy, alluterine fibroids are removed in one stroke.

In 1995, it was demonstrated that fibroids, in a uterus that containedone or multiple fibroids, could be treated without hysterectomy using anon-surgical therapy, specifically comprising bilateral intraluminalocclusion of the uterine arteries (Ravina, et al., “ArterialEmbolization to Treat Uterine Myomata,” Lancet, Sep. 9, 1995; Vol. 346;pp. 671-672, incorporated by reference in its entirety herein). Thistechnique is known as “uterine artery embolization.” The technique usesstandard interventional radiology angiographic techniques and equipment,whereby the uterine arteries are accessed via a transvascular route froma common femoral artery into the left and right uterine arteries.

Three facts explain the success of uterine artery embolization. First,it has been established that pelvic bleeding from a wide variety ofsources (e.g., auto accidents, surgical errors, and post partumhemorrhage) can be effectively controlled with embolization techniquesusing coils placed in arterial and venous lumens (U.S. Pat. Nos.4,994,069, 5,226,911, and 5,549,824, all of which are incorporated intheir entireties herein) (available from Target Therapeutics), orparticles (GELFOAM pledgets, available from Upjohn, Kalamazoo, Mich., orIVALON particles, available from Boston Scientific).

Second, fibroids live a tenuous vascular life with very little abilityto recruit a new blood supply from the host when the primary bloodsupply is compromised. Third, the uterus has a dual (or redundant) bloodsupply; the primary blood supply is from the bilateral uterine arteries,the secondary blood supply from the bilateral ovarian arteries.

Consequently, when both uterine arteries are occluded, i.e., bilateralvessel occlusion, the uterus and the fibroids contained within theuterus are both deprived of their blood supply. However, as demonstratedby Ravina, et al., the effect on the fibroid is greater than the effecton the uterus. In most instances, the fibroid withers and ceases tocause clinical symptoms.

The uterine artery embolization technique utilized by Ravina, et al.uses standard transvascular equipment, available in a typicalinterventional radiology angiography suite. This equipment includesguide catheters to selectively enter the tortuous right and left uterinearteries, Ivalon or Gelfoam particles, and intravascular coils. Withskill and these standard angiographic tools, the uterine arteries can beoccluded bilaterally and fibroid disease treated through a 2 mm hole inthe right groin and through the right common femoral artery. Followingthe procedure, the arterial puncture site is held with manual pressurefor fifteen minutes. While post-procedural pain is often significant,and requires intravenously delivered pain medication, the patient istypically fully recovered in a number of days.

The problem with uterine artery embolization is simple. The physicianswho know how to do the procedure are interventional radiologists, who donot take care of gynecology problems. The physicians who take care ofgynecology problems do not possess the skill necessary to performcatheter-based uterine artery embolization. Accordingly, only on theorder of tens of thousands of uterine artery embolizations have beenperformed, worldwide, since approximately 1995, whereas hundreds ofthousands of hysterectomies have been performed each year for uterinefibroids which are symptomatic.

Currently, many physicians continue to embolize the uterine artery withPVA particles. As reported by the Society for Cardiovascular andInterventional Radiology in late 1999, some 6000 cases have beenperformed within the United States. Currently the annualized run ratefor this procedure is approximately 4500 cases per year.

Previously, physicians have permanently, surgically ligated the uterineartery utilizing metal vascular clips. This procedure has been performedlaparoscopically and requires a great deal of surgical skill to access,identify, dissect, and ligate the uterine arteries. This requirement forhigh skill and a full surgical approach has limited the use of surgicalligation of the uterine arteries as a clinical alternative for uterinefibroid treatment.

The current treatments offered to women focus on permanent or nearpermanent occlusion methods for the uterine artery. These methodsinclude (the expected longevity of the embolic agent is givenparenthetically): embolizing with PVA particles (6 months to permanentin situ); embolizing with stainless steel coils (permanent in situ);embolizing with Gelfoam (3 to 4 weeks before degradation of the embolicparticles); surgical ligation with metal vascular clips (permanent); andsurgical ligation with RF ablation (permanent).

All of the prior art devices and methods are therefore aimed atpermanent occlusion of the uterine artery, resulting in redirection ofthe blood flow to the uterus through collateral circulation. Thepatients who suffer most dramatically from uterine myomata are women ofchild bearing age who may desire to bear additional children. Thecurrent methods of embolizing or ligating uterine arteries arespecifically contraindicated for women who desire to bear additionalchildren. This is the realization of inadequate blood supply to theuterus because of the loss of the uterine arteries, the primary bloodsupply. A few reports have been cited of women who have undergoneuterine artery embolization with PVA particles and then gone on tobecome pregnant and deliver normal babies. Reports have also been citedof women who have experienced premature menopause due to ovarian failurefrom these same procedures.

While it is apparent that uterine artery embolization with the currentembolic agents or ligation techniques is effective for treating uterinemyomata, it is also apparent from a review of case reports andcomplications that this treatment is in need of a substantialimprovement in safety.

The tissue of the vaginal wall is very elastic, pliable, and flexible.The vaginal wall can be made to assume different shapes without tearingand without significant patient discomfort or pain. Heretofore, thisinherent characteristic of these tissues has not been utilized in thetreatment of myomata, or for accessing the uterine artery. Instead,prior techniques have relied upon transvascular routes (Ravina, et al.),complete surgical or laparoscopic dissection of the tissues surroundinga uterine artery to achieve access to the vessel. The difficulty andcost associated with the use of traditional transvascular access, andthe possibility of infection and surgical complication associated withdissection, render these prior techniques unacceptable.

Those of skill in the art are well acquainted with DUB, PPH, andcesarian section-related bleeding. While the causes of DUB are often notidentified, current treatments include endometrial ablation andhysterectomy, which can be extreme treatments for some patients. PPH andcesarian section-related bleeding can be a dangerous if not quickly andadequately controlled, which may require a fast surgical response, fromwhich the patient may suffer from associated trauma of the surgery.

Another aspect of hysterectomy procedures is that the blood supply tothe uterus is typically stopped by ligating the uterine arteries, toprevent the patient from bleeding excessively as the uterus is removed.This ligation task can be very laborious and time-consuming, as thearteries are dissected and ligated by the surgeon, and have associatedcomplications.

There therefore still remains a need in the art for improvements inmethods, processes, and techniques for occluding the uterine arteriesfor treatment of numerous conditions and/or facilitating otherprocedures.

SUMMARY OF THE INVENTION

According to a first exemplary embodiment, a process of treating acondition of a patient comprises the steps of non-invasively,non-permanently occluding a uterine artery for a therapeuticallyeffective time period, and reestablishing blood flow through the uterineartery at the termination of said therapeutically effective time period.

According to a second exemplary embodiment, a process useful fortreating a patient having at least one uterine artery and a uterus, theprocess comprises the steps of non-invasively, non-permanently occludingat least one uterine artery for a therapeutically effective time periodand removing at least a portion of a uterus of a patient.

Still other objects, features, and attendant advantages of the presentinvention will become apparent to those skilled in the art from areading of the following detailed description of embodiments constructedin accordance therewith, taken in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention of the present application will now be described in moredetail with reference to preferred embodiments of the apparatus andmethod, given only by way of example, and with reference to theaccompanying drawings, in which:

FIG. 1 illustrates a perspective view of portions of a uterus, vagina,uterine arteries, and an exemplary tool;

FIG. 2 illustrates a right side elevational view of portions of auterus, vagina, uterine arteries, and an exemplary tool according to anexemplary embodiment of the invention;

FIG. 3 illustrates a cross-sectional view taken at line 3-3 in FIG. 2;

FIG. 4 illustrates a front elevational view of portions of a uterus,vagina, uterine arteries, and an exemplary tool;

FIG. 5 illustrates a cross-sectional view taken at line 5-5 in FIG. 4;

FIG. 6 illustrates a right side elevational view of portions of auterus, vagina, uterine arteries, and an exemplary tool, during aclamping step;

FIG. 7 illustrates a cross-sectional view taken at line 7-7 in FIG. 6;

FIG. 8 illustrates a front elevational view of portions of a uterus,vagina, uterine arteries, and an exemplary tool, similar to FIG. 4,during a clamping step;

FIG. 9 illustrates a cross-sectional view taken at line 9-9 in FIG. 8;

FIG. 10 illustrates a right side elevational view of portions of auterus, vagina, uterine arteries, and an exemplary tool according toanother exemplary embodiment of the invention; and

FIG. 11 illustrates a cross-sectional view taken at line 11-11 in FIG.10.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Non-permanent occlusion of the uterine artery is sufficient to cause thedemise of uterine myomata without unnecessarily exposing other tissuesand anatomical structures to hypoxia attendant to prior permanentocclusion techniques. Burbank, Fred, et al., Uterine Artery Occlusion byEmbolization or Surgery for the Treatment of Fibroids: A UnifyingHypothesis-Transient Uterine Ischemia, The Journal of the AmericanAssociation of Gynecologic Laparoscopists, November 2000, Vol. 7, No. 4Supplement, pp. S3-S49. While occlusion of a uterine artery can beachieved using procedures which penetrate tissue of the patient, theinventors herein have discovered that occlusion of one or both of theuterine arteries of a patient can be achieved non-invasively, that is,without penetrating tissue of the patient.

In the context of the present invention, a therapeutically effectivetransient time of occlusion of a uterine artery to treat uterine fibroidtumors is from 1 hour to 1 day (24 hours). Also in the context of thepresent invention, a therapeutically effective temporary time ofocclusion of a uterine artery to treat uterine fibroid tumors is from 1day (24 hours) to 7 days (168 hours), and preferably is about 3-4 days(72-96 hours).

Methods for non-permanent uterine artery occlusion in accordance withthe present invention allow for substantial improvements in safety andefficacy of this procedure over prior techniques. Processes inaccordance with the present invention preferably result in death to theentire uterine fibroid cell line, a normal blood supply to the uteruswithin a short period of time after reestablishment of the blood supplythrough the uterine artery or arteries, preferably about a week, and nofear of premature menopause and ovarian failure due to particulateembolization of the ovarian artery or ovaries.

Methods for non-permanent uterine artery occlusion of the presentinvention are all aimed at producing the following events, preferably inthe sequence indicated; Blood flow in the uterine artery is slowed orstopped by occluding the artery. This stoppage of blood flow creates aclotting cascade within the artery in a fashion well known to thoseskilled in the art. Once blood flow has ceased and the vessel is filledwith blood clots or thrombus, uterine fibroids, and more particularlythe cells of the uterine fibroids, suffer a nearly immediate deathbecause of the cessation of blood flow to them. The uterus becomesanoxic, but is partially supplied by the ovarian arteries and othercollateral circulation. This collateral circulation is adequate to keepthe uterine tissues alive and allow for it to recover as the total bloodflow to the uterus returns to normal.

The thrombus formed within the transiently or temporarily occluded bloodvessel is addressed by the blood system with a series of enzymes whichattempt to lyse the thrombus. This cycle is predictable and effective,and it can be assisted with various thrombolytic agents such as tissueplasminogen activator (tPA). In order to assure that the thrombus iswell formed to occlude the uterine artery in accordance with theprocesses of the present invention, hemostasis should be maintained forat least about 1 hour to about 24 hours. Therefore, it is preferablethat the mechanism which initiates formation of the thrombus, describedin greater detail below, stays in place at least 1 hour to 24 hours toprovide for the death of the fibroid cell line. After this initialperiod to initiate and maintain the formation of a thrombus in theartery, preferably about 1-24 hours, the mechanism can be removed. Asdescribed in greater detail below, the mechanism for occluding theuterine artery can take any one of a number of forms in accordance withthe present invention, and therefore can be removed by a number of ways,including physical removal from the artery. As will be readilyappreciated by one of ordinary skill in the art, the present inventionis not limited to the specific examples herein of mechanisms which areuseful for occluding a uterine artery, and other suitable methods anddevices are also within the spirit and scope of the present invention.

Without being limited to a particular theory, the inventors hereinbelieve that the efficacy of the present invention is due, at least inpart, to its emulation of what may have been a natural phenomenon, atleast among female humans. In the distant past, it is likely that womengenerally were pregnant much more than is common today, and would havegone through the birthing process and delivery more often and/or morefrequently than today. As is well known to those of skill in the art,when the placenta separates from the uterine wall during childbirth, thewoman does not (usually) suffer from massive bleeding, even though thehuge number of blood vessels connecting the uterus and the placenta haveabruptly been severed. Instead, a biological mechanism, which is notwell understood, initiates rapid clotting in the blood vessels which hadbeen supplying the placenta with blood, and the bleeding stops.

Upon this massive clotting event, a region of the uterus through whichthese blood vessels extend is also starved of blood, becoming hypoxic oranoxic. Thus, any fibroids which are also located in this region of theuterus are also starved of blood, and are killed, as described herein.With the historical expectation that women were pregnant and wentthrough childbirth more frequently, and the common understanding thatthe location of implantation of a fertilized ova in the uterine wall(endometrium) is essentially random, the result is that, over the timeperiod during which a woman can become pregnant, a set of regions of theuterus are cleared of fibroids. Thus, the relatively recent increase inthe diagnosis of myomata may be attributable, at least in part, to the(expected) fact that women are pregnant less, and less frequently, andlive longer, than historically was the case. Within this framework, theskilled artisan will appreciate that the present invention emulates, ina sense, the biology of childbirth by causing a portion of the uterus,or the entire uterus, to become hypoxic or anoxic.

Steps of methods in accordance with the present invention will now bedescribed with reference to exemplary mechanisms which occlude one orboth uterine arteries in order to initiate the clotting cascade whichresults in thrombus formation. As will be readily apparent to one ofordinary skill in the art, the devices illustrated and described hereinare merely exemplary, and numerous devices can be used to perform themethods of the present invention. Thus, while the drawing figuresillustrate several types of devices, detailed descriptions of theirstructures have not been included herein because the exact nature ofdevices are not critical to performance of the methods according to thepresent invention.

While it is likely sufficient that the use of only one of the followingmodalities will result in the occlusion of a uterine artery, it is alsowithin the scope of the present invention to simultaneously or seriallyemploy multiple modalities to occlude a single uterine artery.

The following are merely provided by way of example and not oflimitation. Access to the uterine arteries is preferably achieved byinvagination of the vaginal wall without significant, and preferablywithout any, penetration of the patient's tissues, including the vaginalwall.

One or both of the uterine arteries of the patient are occluded usingone of the devices and associated procedures described below. Theadequacy of the occlusion can then optionally be measured by any processsuitable for the measurement of blood flow, e.g., Doppler ultrasound.The time of initial occlusion can then optionally be marked so that thetotal time of occlusion of the artery can be ascertained. Although it ispreferable that both of the patient's uterine arteries are occluded forthe minimum time periods necessary to initiate thrombus formation, andmore preferable that the occlusion times for both arteries overlap by atleast this minimum time, it is also within the scope of the presentinvention to occlude the uterine arteries serially.

In the context of the present invention, the term “non-invasive” meansthat tissue or tissues of the patient, on whom the methods of thepresent invention are performed, are not significantly penetrated, andpreferably are not penetrated at all. Thus, “non-invasive” also includessituations in which minor, including incidental, abrasions, lacerations,and the like occur, without purposefully penetrating tissue in order toaccess the anatomical structure of interest. As such minor penetrationsof tissue are commonplace in the medical and surgical arts and are notconsidered to be invasive, the skilled artisan will readily appreciatethe use of the term “non-invasive” in the context of the presentinvention.

Turning now to the drawing figures, FIGS. 1-11 illustrate portions of auterus of a patient and some of her adjacent anatomical structures,reference to which can be made for a better understanding of the presentinvention. The drawing figures diagrammically illustrate a uterus 10which is afflicted with one or more fibroid tumors 22. The patient'svagina 12 includes the vaginal fornix 14. The cervix 20 extends betweenthe uterine cavity (not illustrated) and the vagina 12. As discussedfurther herein, the uterine arteries 16 a, 16 b extend to the uterus 10and supply the uterus (and the fibroids) with oxygenated blood.

While one of ordinary skill in the art will appreciate that uterinearteries' internal diameters will normally vary within groups ofpatients, and therefore that the present invention relates tonon-permanent occlusion of uterine arteries of various sizes, typicallyuterine arteries have internal diameters of about 2 mm to about 4 mmprior to (upstream of) the first order branches of the artery at theuterus. The first order branches, typically, have internal diameters ofless than 2 mm, with higher order branches having again smaller internaldiameters.

The inventors herein have found that the uterine arteries are located,for female humans, adjacent to the vaginal wall, and more specificallyare typically within about 2 cm from the vaginal wall at the vaginalfornix 14. This characteristic of the anatomy had not previously beenidentified in the literature. Furthermore, the inventors herein havediscovered that the distance between the vaginal wall (at the fornix)and a uterine artery is shortened upon traction being applied to thecervix 20 in a direction toward the vaginal opening, such as by pullingon the cervix with, e.g., tenaculum or the like. The inventors hereinhave also discovered that upon invagination of the vaginal wall asdescribed herein, the distance between this part of the uterine arteries16 a, 16 b, and the vaginal wall decreases. By way of example and not oflimitation, it has been observed by the inventors herein that thisdistance can be decreased to about 1 cm or less. This decrease in thedistance between a uterine artery and the vaginal wall can greatlyfacilitate the methods of the present invention by increasing thelikelihood that the uterine artery of interest can be accessed, evenwithout the aid of location and identification devices such asultrasound, Doppler ultrasound, MRI, CAT, and the like.

Therefore, while the processes in accordance with the present inventioncan be performed on a uterine artery prior to the first order branches,the present invention also can be performed on higher order brancheswith smaller diameter blood vessels. Thus, while the followingdescriptions reference the uterine artery, the term uterine artery alsoincludes higher order branches of the uterine artery and thenon-permanent occlusion of them. As illustrated in the drawing figures,the uterine arteries 16 a, 16 b extend generally laterally from theouter portions of the uterus in positions close to the vaginal fornix14.

It has been observed and reported that blood vessel hemostasis ofgreater than 4 days (96 hours) is necessary to permanently occlude ablood vessel. See Hay, D. L., et al., Hemostasis in blood vessels afterligation,” Am. J. Obstet. Gynecol. 160:3; pp. 737-739 (March 1989), andBrohim, R. M., et al., “Development of independent vessel security afterligation with absorbable sutures or clips,” Am. J. Surg., Vol. 165, pp.345-349 (March 1993), the entire contents of both of which areincorporated by reference in their entireties herein. Thus, as theprocesses in accordance with the present invention are directed tonon-invasive, non-permanent, transient and/or temporary occlusion of theuterine arteries, it is necessary to remove the vessel occlusion at atime prior to the artery closing permanently and after a therapeuticallyeffective time period of hemostasis for the uterine fibroid cell line tohave died from the lack of a sufficient blood supply.

TRANSIENT OCCLUSION

After at least 1 hour of occlusion, preferably 1-24 hours, morepreferably 4-24 hours, of total occlusion time for a uterine artery, thedevice, mechanism, or modality by which the artery was occluded isremoved, permitting reestablishment of the blood flow through theuterine artery to the uterus. A therapeutically effective transient timeof occlusion of a uterine artery to treat uterine fibroid tumors is from1 hour to 1 day (24 hours). By occluding a uterine artery for atherapeutically effective transient time of occlusion, the blood flowthrough the uterine artery is slowed sufficiently, and preferablystopped, for a time sufficient for a blood clot to form in the vesselsof the uterus and fibroids growing on the uterus. Once the blood clot isformed, the clot itself can assume the task of slowing or stopping bloodflow through the uterine artery, and the device, mechanism, or modalitywhich initially slowed or stopped blood flow (described in greaterdetail below) can be removed. As will be readily appreciated by one ofordinary skill in the art, the clot will then begin to be broken down orlysed by the body. This lysing process can optionally be assisted by asystemic or localized administration of a thrombolytic agent, such astPA, or the like, if the practitioner elects to do so.

TEMPORARY OCCLUSION

After at least 1 day (24 hours), preferably 1-7 days, more preferably3-4 days, of total occlusion time for a uterine artery, the device,mechanism, or modality by which the artery was occluded is removed,permitting reestablishment of the blood flow through the uterine arteryto the uterus. Different from transient occlusion discussed above,temporary occlusion does not rely solely on the blood clot formed as aresult of the slowing or stoppage of blood flow through the uterineartery. In accordance with the present invention, temporary occlusionbenefits from the combination of both the device, mechanism, or modalityand the blood clot to limit or stop blood flow through the uterineartery.

In addition to the foregoing steps in the processes of the presentinvention, removal of a blood clot or thrombus can be accelerated by theuse of an agent which lyses the clot, including the administration oftPA to the patient after the therapeutically effective time period.

Turning again to the drawing figures, FIGS. 1-5 illustrate a stepaccording to one exemplary method in accordance with the presentinvention. As can be seen in FIG. 1, the vaginal wall, because of itsinherent elasticity and flexibility, permits a simple clamping tool 100to invaginate the vaginal wall. The vaginal wall is invaginated towardthe uterine artery 16 b on two lateral sides of the uterine artery,corresponding to the distalmost ends of the two clamping portions 102 a,102 b of the tool 100. The portions 102 a, 102 b are preferablyadvanced, and invaginate the vaginal wall, in an open position andspaced apart from each other a distance large enough so that the uterineartery 16 b can be positioned between the ends of the clamping portions.

Although not necessary for performance of the methods of the presentinvention, location of the uterine artery 16 b, and verification thatthe uterine artery is between the ends of the clamping portions 102 a,102 b, can be assisted through the use of commonplace imaging andlocating tools, such as MRI, fluoroscopy, CAT, ultrasound, Dopplerultrasound, and the like, as will be readily appreciated by one ofordinary skill in the art. As blood flow sensor 103 is shownschematically in FIG. 9. The present invention includes, however,methods wherein the practitioner does not use or rely on such additionaltools, and positions the tool 100 relative to the uterine artery 16 bbased upon the practitioner's knowledge and experience of where theuterine artery is relative to other anatomical features of the patient.

FIGS. 6-9 illustrate a step of an exemplary method in accordance withthe present invention after the step illustrated in FIGS. 1-5. In thelater step of FIGS. 6-9, the tool 100 has been closed onto the properlypositioned uterine artery 16 b, and the uterine artery is collapsed bythe bilateral force exerted on the uterine artery. More particularly,the portions 102 a, 102 b exert a combined clamping force on theinvaginated vaginal walls 18 a, 18 b, which exert forces on any tissuebetween the walls 18 a, 18 b, which in turn exert forces on the exteriorwall of the uterine artery 16 b. The force(s) exerted on the wall of theuterine artery are sufficient to collapse the uterine artery, and atleast reduce the blood flow rate through the uterine artery to a levelsufficient to initiate a clotting sequence. Optionally, the Wall of theuterine artery 16 b can be completely collapsed, i.e., the blood flowthrough the uterine artery is zero. As described elsewhere herein,cessation of blood flow through the uterine artery can have therapeuticeffects for treating fibroids.

Tool 100 can be any device which can invaginate the vaginal wall asdescribed above, and clamp or press the invaginated vaginal wall to atleast partially collapse the uterine artery between the clampingportions of the tool.

FIGS. 10 and 11 illustrate a step of yet another exemplary method inaccordance with the present invention. A tool 200 is used to invaginatethe vaginal wall at 18 c, and to press against the uterine artery 16 bwith an end portion 202. As described above, the uterus 10 is oftentimesa fairly muscular, moderately rigid structure. The inventors herein havediscovered that the uterus can be used as the second force-exertingmember or anvil by which the uterine artery can be collapsed. In thefirst exemplary embodiment, described above, the two force originatingmembers were portions of a tool 100; in the second exemplary embodiment,the tool 200 is one of the force-originating members, and the uterusitself is the other force-originating member. In this context, theuterus 10 can be likened to an anvil or platen against which a toolpresses the uterine artery 16 b to collapse it. Thus, tool 200 shouldhave an end 202 which is sufficiently large that, upon invagination ofthe vaginal wall 18 c, the uterine artery 16 b can be at least partiallycollapsed. Of course, tool 200 should not be so large that it isincapable of being inserted into the vaginal fornix 14.

Tool 200 can be any device which can invaginate the vaginal wall asdescribed above, and clamp or press the invaginated vaginal wall 18 c toat least partially collapse the uterine artery between the tool and theuterus 10.

The present invention also relates to the treatment of conditions whichinvolve or include uterine bleeding, and more specifically to inhibitingor stopping uterine bleeding altogether. As discussed briefly above,there are numerous known conditions which involve or include uterinebleeding; DUB, PPH, and obstetrical, including cesarian section-related,hemorrhaging, and bleeding during and after a myomectomy, are but a fewexamples of uterine bleeding which can be inhibited or stopped bymethods of the present invention. As described above, the collapse of auterine artery and the associated hemostasis in the artery will reduceor completely cut off the blood supply to a portion of the uterus;simultaneous collapse of both uterine arteries in a patient reduces orcompletely cuts off the blood supply to the uterus, and therefore stopsuterine bleeding, whatever the cause.

Thus, the present invention extends to any procedure which can benefitfrom a reduction in the blood flow to and in the uterus of a patient,including a complete cessation of blood flow. As discussed above, it maybe appropriate in some procedures, such as hysterectomy, to eventuallypermanently stop the blood flow through the uterine artery. According tocertain aspects of the present invention, hysterectomy can befacilitated by first occluding the uterine artery using methods of thepresent invention, and thereafter proceeding with other steps of thehysterectomy. As methods of the present invention benefit from thepossibility of being rapidly performed, in contrast to the laborious andtime-consuming tasks of dissection and ligation of the uterine arteriestypically involved with hysterectomy procedures, the entire hysterectomyprocedure can be less time consuming. According to thishysterectomy-related embodiment of the present invention, the termtherapeutically effective time means the time until the blood flowthrough the uterine artery is controlled by another modality, such as bypermanent ligation of the uterine artery by known techniques. Otherprocedures to which the methods of the present invention will be readilyapparent to those of skill in the art.

As will be readily appreciated by those of skill in the art, it canoften be the case that a particular procedure or treatment of a patient,although indicated, is not fully successful in treatment of thepatient's condition, and another procedure or treatment is indicated andadvisable. In the context of the present invention, there may beinstances when non-permanent occlusion of one or both uterine arteriesof a patient does not fully alleviate the patient's symptoms and, uponconsultation with the medical practitioner, the patient may elect andconsent to myomectomy, or partial or complete hysterectomy. Thus, thepresent invention also extends to methods of performing a myomectomyand/or a hysterectomy, in any form, which are preceded by a step orsteps of non-permanent occlusion of a uterine artery, as describedherein, well before the myomectomy or hysterectomy.

The foregoing exemplary embodiments of methods in accordance with thepresent invention are performed on one or all uterine arteries 16 a, 16b of the patient. According to the present invention, the same ordifferent specific methods can be performed on different uterinearteries, e.g., bilateral occlusion on uterine artery 16 a andunilateral occlusion on uterine artery 16 b, or bilateral or unilateralocclusion on both uterine arteries.

While the invention has been described in detail with reference topreferred embodiments thereof, it will be apparent to one skilled in theart that various changes can be made, and equivalents employed, withoutdeparting from the scope of the invention. While specific reference hasbeen made to female adult human patients, processes in accordance withthe present invention also include occlusion of one or both of theuterine arteries of any female patient that has uterine arteries,including pediatric humans and other mammals, and in particularnon-marsupial mammals. Each of the aforementioned published documentsare incorporated by reference herein in their entirety.

1. A process of treating a female patient's uterus, comprising: at leastpartially occluding a uterine artery of the patient for atherapeutically effective time period by applying pressure to theuterine artery through a wall of a vaginal fornix of the patient; andre-establishing blood flow through the uterine artery at the terminationof said therapeutically effective time period by releasing the pressureapplied to the uterine artery through vaginal wall.
 2. A process inaccordance with claim 1, further comprising: invaginating a portion of avaginal wall of a patient prior to applying pressure to the uterineartery to at least partially occlude the uterine artery.
 3. A process inaccordance with claim 2, wherein the invaginating a portion of thevaginal wall extends the vaginal wall adjacent to the uterine artery tobe occluded.
 4. A process in accordance with claim 3, whereininvaginating a portion of the vaginal wall comprises invaginating twoportions of the vaginal wall so that the vaginal wall extends adjacentto the uterine artery on opposite sides of the uterine artery.
 5. Aprocess in accordance with claim 2, wherein invaginating a portion ofthe vaginal wall comprises invaginating a portion of the vaginal wall sothat the vaginal wall extends under and immediately adjacent to theuterine artery.
 6. A process in accordance with claim 1, whereinoccluding the uterine artery comprises collapsing said uterine arteryeffective to stop blood flow through said uterine artery.
 7. A processin accordance with claim 6, wherein collapsing said uterine arterycomprises clamping said uterine artery.
 8. A process in accordance withclaim 7, wherein clamping said uterine artery comprises bilaterallyclamping said uterine artery.
 9. A process in accordance with claim 6,wherein collapsing said uterine artery comprises compressing saiduterine artery between a tool on a first side of said uterine artery andan anatomical structure on a second side of said uterine artery oppositesaid first side of said uterine artery.
 10. A process in accordance withclaim 1, wherein said therapeutically effective time period is between 1hour and 168 hours.
 11. A process in accordance with claim 1, whereinsaid therapeutically effective time period is between 1 hour and 24hours.
 12. A process in accordance with claim 1, wherein saidtherapeutically effective time period is between 24 hours and 168 hours.13. A process in accordance with claim 1, wherein said therapeuticallyeffective time period is between 72 hours and 96 hours.
 14. A process inaccordance with claim 1, wherein the therapeutically effective timeperiod is to treat uterine fibroids.
 15. A process in accordance withclaim 1, wherein the therapeutically effective time period is to treat acondition selected from the group consisting of DUB, PPH, bleeding fromcesarian section surgery, and bleeding associated with myomectomy.
 16. Aprocess in accordance with claim 1, wherein two uterine arteries areoccluded for the therapeutically effective time period.
 17. A processuseful for treating a condition of a patient having at least one uterineartery and a uterus, comprising: non-invasively occluding at least oneuterine artery for a therapeutically effective time period; and removingat least a portion of a uterus of a patient.
 18. An assembly fortreating a uterine disorder of a female patient by occluding at least inpart a uterine artery thereof, comprising: a) a first clamping memberwhich has a distal section forming in part a jaw having a pressureapplying clamping surface on a distal end of the jaw that is configuredto invaginate vaginal tissue of the patient's vaginal fornix and thathas sufficient area to occlude the patient's uterine artery when pressedagainst invaginated tissue of the patient's vaginal fornix; b) a secondclamping member which has a distal section forming in part a jaw havinga pressure applying clamping surface on a distal end of the jaw inopposition to the pressure applying clamping surface on the distal endof the jaw of the first clamping member that is configured to invaginatevaginal tissue of the patient's vaginal fornix and that has sufficientarea to occlude the patient's uterine artery when pressed againstinvaginate tissue of the patient's vaginal fornix; c) a pivotalconnection between the first and second clamping members at a locationproximally spaced from the pressure applying surfaces of the first andsecond clamping members; and d) a blood flow sensor to detect thepatient's uterine artery.
 19. The assembly of claim 18, wherein theblood flow sensor is a Doppler ultrasound sensor.
 20. The assembly ofclaim 18, wherein the distal ends of the jaws of the first and secondclamping members are configured to invaginate a vaginal wall and clampat least a portion of said vaginal wall between jaws thereof and to atleast partially occlude a uterine artery disposed therein.
 21. Theassembly of claim 18, wherein the clamping members are formed at leastin part of a resorbable material.
 22. The assembly of claim 21, whereinthe resorbable material comprises polyglycolic acid.
 23. The assembly ofclaim 21, wherein the resorbable material comprises a dissolvablematerial selected from the group consisting of as polyvinyl alcohol andgelatin.
 24. The device of claim 18 wherein the blood flow sensor isconfigured to verify that the patient's uterine artery is locatedbetween the jaws of the first and second clamping members.
 25. Thedevice of claim 18 wherein the first and second clamping members havetissue receiving recesses proximal to the jaws thereof.
 26. The assemblyof claim 18 wherein at least the first clamping member has a proximalsection forming in part a manually manipulative handle configured toextend out of the patient's vagina when the device is in position toocclude the patient's uterine artery.
 27. The assembly of claim 26wherein the second clamping member has a proximal section forming inpart a manually manipulative handle configured to extend out of thepatient's vagina when the device is in position to occlude the patient'suterine artery.